A Genomic Regulatory Element That Directs Assembly and Function of Immune-Specific AP-1–IRF Complexes

Citations Over TimeTop 1% of 2012 papers

Abstract

Interferon regulatory factor 4 (IRF4) and IRF8 regulate B, T, macrophage, and dendritic cell differentiation. They are recruited to cis-regulatory Ets-IRF composite elements by PU.1 or Spi-B. How these IRFs target genes in most T cells is enigmatic given the absence of specific Ets partners. Chromatin immunoprecipitation sequencing in T helper 17 (T(H)17) cells reveals that IRF4 targets sequences enriched for activating protein 1 (AP-1)-IRF composite elements (AICEs) that are co-bound by BATF, an AP-1 factor required for T(H)17, B, and dendritic cell differentiation. IRF4 and BATF bind cooperatively to structurally divergent AICEs to promote gene activation and T(H)17 differentiation. The AICE motif directs assembly of IRF4 or IRF8 with BATF heterodimers and is also used in T(H)2, B, and dendritic cells. This genomic regulatory element and cognate factors appear to have evolved to integrate diverse immunomodulatory signals.

Related Papers

• → Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression(2002)319 cited
• → PU.1 cooperates with IRF4 and IRF8 to suppress pre-B-cell leukemia(2016)65 cited
• → IRF4 and IRF8: governing the virtues of B lymphocytes(2014)59 cited
• → A Comprehensive Analysis of Interferon Regulatory Factor Expression: Correlation with Immune Cell Infiltration and Patient Prognosis in Endometrial Carcinoma(2022)6 cited
• → Interferon Regulatory Factor 4(2020)